Cited by 281Adrenal and Paraganglionic TumorsAdrenal Hormones and DisordersHormonal Regulation and Hypertension

The DOI matches its Crossref record; 111 of the 122 references it cites were found in a registry or an index; 1 of the 207 sources its claims cite were checked for support.

Diagnosis and Treatment of Subclinical Hypercortisolism

Open access
Chiodini, Iacopo·2011·The Journal of Clinical Endocrinology & Metabolism

Abstract

Context: Subclinical hypercortisolism (SH) is a condition of biochemical cortisol excess without the classical signs or symptoms of overt hypercortisolism. It is thought to be present in the 5–30% of patients with incidentally discovered adrenal mass (adrenal incidentalomas), which in turn are found in 4–7% of the adult population. Therefore, SH has been suggested to be present in 0.2–2.0% of the adult population. Some studies suggested that this condition is present in 1–10% of patients with diabetes or established osteoporosis. The present manuscript reviews the literature on diagnostic procedures and the metabolic effect of the recovery from SH. Evidence Acquisition: A PubMed search was used to identify the available studies. The most relevant studies from 1992 to November 2010 have been included in the review. Evidence Synthesis: The available data suggest that SH may be associated with chronic complications, such as hypertension, diabetes mellitus, overweight/obesity, and osteoporosis. The available intervention studies suggest that the recovery from SH may lead to the improvement of hypertension and diabetes mellitus. A retrospective study suggests that this beneficial effect could be predicted before surgery. Conclusions: SH is suggested to be associated with some chronic complications of overt cortisol excess. Recovery from this condition seems to improve these complications. However, a large, prospective, randomized study is needed to confirm this hypothesis and to establish the best diagnostic approach to identify patients with adrenal incidentalomas who can benefit from surgery.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review summarizes the diagnosis, prevalence, and management of subclinical hypercortisolism (SH), defined as biochemical cortisol excess without classical signs or symptoms of overt hypercortisolism. It concludes that no consensus or gold standard exists for diagnosis, that the DST-UFC-ACTH combination is the best available compromise, and that surgery may improve metabolic complications but evidence remains limited.

Key findings

  • SH is estimated to be present in 5–30% of patients with adrenal incidentalomas (AI); because AI are found in 4–7% of adults, SH may be present in 0.2–2.0% of the adult population, and in 1–10% of patients with diabetes or established osteoporosis.
  • No single HPA-axis parameter has adequate sensitivity and specificity. In one scintigraphy-validated study, the 1-mg DST cutoff of 3.0 μg/dl showed the best compromise (sensitivity 63%, specificity 75%); in 231 AI patients, the DST-UFC-ACTH combination criterion had sensitivity 61.9%, specificity 77.1%, and accuracy 75.8% for predicting a cluster of complications.
  • Prevalence in at-risk groups varied: 10.8% in 294 type 2 diabetic inpatients; 4.8% in osteoporosis and 10.8% in osteoporosis with vertebral fractures. SH appears more commonly of adrenal than pituitary origin.
  • In the only prospective randomized study cited (23 surgically treated, 22 conservatively treated), surgery improved hypertension, diabetes, obesity, and dyslipidemia in 66.7%, 62.5%, 50%, and 37.5% of cases, respectively; conservative management worsened hypertension, diabetes, and dyslipidemia in 80%, 33.3%, and 20%.

Methods

  • Narrative clinical review of the literature on diagnostic procedures and the metabolic effects of recovery from SH.
  • Synthesizes studies of patients with adrenal incidentalomas and at-risk populations (diabetes, osteoporosis), including diagnostic accuracy studies and surgical versus conservative treatment/follow-up studies; tables summarize HPA-axis alterations, diagnostic accuracy, prevalence, and outcomes.
  • Main analysis is qualitative synthesis; no new primary data or meta-analysis are presented.

Limitations

  • The paper states there is no consensus on clinical or biochemical criteria for SH, no clinical gold standard, and that cortisol secretion is a continuum and highly variable; ACTH and 24-h UFC reliability is low, comorbidities and medications affect the DST, and salivary cortisol methods are not standardized.
  • The paper states that no large prospective randomized trial has compared surgical versus conservative treatment, available studies are small and often retrospective or nonrandomized, and data on hard endpoints and cost-effectiveness are lacking.
  • Evident from the text: as a single-author narrative review, it draws on heterogeneous studies with differing cutoffs, assays, and outcome definitions, which limits comparability across findings.

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Integrity signals

Registry

Crossref · 10.1210/jc.2010-2722

Cites

111 of 111 references verified0 citation errors · 0 not checkable

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Metadata

Authors
Chiodini, I.
Affiliations
University of Milan (IT)
Corresponding author
Chiodini, Iacopo
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2011-05-01
Volume
96
Issue
5
Pages
1223-1236
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2068496880
Cited by
279
References
122
Citations by year
2026: 6 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 10 · 2021: 23 · 2020: 22 · 2019: 21 · 2018: 27 · 2017: 21 · 2016: 19 · 2015: 28 · 2014: 19 · 2013: 24 · 2012: 27
FWCI
4.63
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
Keywords
subclinical hypercortisolism, adrenal incidentaloma, cortisol excess, hypertension, diabetes mellitus, osteoporosis, obesity, adrenal surgery, metabolic recovery
MeSH terms
Adrenal Gland Neoplasms, Adult, Child, Cushing Syndrome, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Treatment Outcome

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